Clay-based hemostatic agents

ABSTRACT

A hemostatic device for promoting the clotting of blood includes a gauze substrate, a clay material disposed on the gauze substrate, and also a polyol such as glycerol or the like disposed on the gauze substrate to bind the clay material. When the device is used to treat a bleeding wound, at least a portion of the clay material comes into contact with blood emanating from the wound to cause the clotting. A bandage that can be applied to a bleeding wound to promote the clotting of blood includes a flexible substrate and a gauze substrate mounted thereon. The gauze substrate includes a clay material and a polyol. A hemostatic sponge also includes a gauze substrate and a dispersion of hemostatic material and a polyol on a first surface of the substrate.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/090,072, filed Apr. 4, 2016, entitled “Clay-Based Hemostatic Agents,”which is a continuation of U.S. patent application Ser. No. 14/185,873,filed Feb. 20, 2014, and issued as U.S. Pat. No. 9,333,117, entitled“Clay-Based Hemostatic Agents and Devices for the Delivery Thereof,”which is a continuation of U.S. patent application Ser. No. 13/759,963,filed Feb. 5, 2013, and issued as U.S. Pat. No. 9,078,782, entitled“Hemostatic Fibers and Strands,” which is a continuation of U.S. patentapplication Ser. No. 13/682,085, filed Nov. 20, 2012, and issued as U.S.Pat. No. 8,846,076, entitled “Hemostatic Sponge,” which is acontinuation of U.S. patent application Ser. No. 13/363,270, filed Jan.31, 2012, and issued as U.S. Pat. No. 8,343,537, entitled “Clay-BasedHemostatic Agents and Devices for the Delivery Thereof,” which is acontinuation of U.S. patent application Ser. No. 12/581,782, filed Oct.19, 2009, and issued as U.S. Pat. No. 8,114,433, entitled “Clay-BasedHemostatic Agents and Devices for the Delivery Thereof,” which is acontinuation of U.S. patent application Ser. No. 11/715,057, filed Mar.6, 2007, and issued as U.S. Pat. No. 7,604,819, entitled “Clay-BasedHemostatic Agents and Devices for the Delivery Thereof,” which is acontinuation-in-part application of U.S. patent application Ser. No.11/590,427, filed Oct. 30, 2006, and issued as U.S. Pat. No. 7,968,114,entitled “Clay-Based Hemostatic Agents and Devices for the DeliveryThereof,” which claims the benefit of U.S. Provisional PatentApplication Ser. No. 60/808,618, filed May 26, 2006, entitled “BloodClotting Compound” and U.S. Provisional Patent Application Ser. No.60/810,447, filed Jun. 1, 2006, entitled “Hemostatic Device withOxidized Cellulose Pad.” The contents of all of the above-referencedapplications are incorporated herein by reference in their entireties.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates generally to agents and devices forpromoting hemostasis and, more particularly, to clay-based hemostaticagents and devices incorporating such agents for the delivery thereof tobleeding wounds.

Description of the Related Art

Blood is a liquid tissue that includes red cells, white cells,corpuscles, and platelets dispersed in a liquid phase. The liquid phaseis plasma, which includes acids, lipids, solublized electrolytes, andproteins. The proteins are suspended in the liquid phase and can beseparated out of the liquid phase by any of a variety of methods such asfiltration, centrifugation, electrophoresis, and immunochemicaltechniques. One particular protein suspended in the liquid phase isfibrinogen. When bleeding occurs, the fibrinogen reacts with water andthrombin (an enzyme) to form fibrin, which is insoluble in blood andpolymerizes to form clots.

In a wide variety of circumstances, animals, including humans, can bewounded. Often bleeding is associated with such wounds. In somecircumstances, the wound and the bleeding are minor, and normal bloodclotting functions in addition to the application of simple first aidare all that is required. Unfortunately, however, in other circumstancessubstantial bleeding can occur. These situations usually requirespecialized equipment and materials as well as personnel trained toadminister appropriate aid. If such aid is not readily available,excessive blood loss can occur. When bleeding is severe, sometimes theimmediate availability of equipment and trained personnel is stillinsufficient to stanch the flow of blood in a timely manner.

Moreover, severe wounds can often be inflicted in remote areas or insituations, such as on a battlefield, where adequate medical assistanceis not immediately available. In these instances, it is important tostop bleeding, even in less severe wounds, long enough to allow theinjured person or animal to receive medical attention.

In an effort to address the above-described problems, materials havebeen developed for controlling excessive bleeding in situations whereconventional aid is unavailable or less than optimally effective.Although these materials have been shown to be somewhat successful, theyare sometimes not effective enough for traumatic wounds and tend to beexpensive. Furthermore, these materials are sometimes ineffective insome situations and can be difficult to apply as well as remove from awound.

Additionally, or alternatively, the previously developed materials canproduce undesirable side effects. For example, one type of prior artblood clotting material is generally a powder or a fine particulate inwhich the surface area of the material often produces an exothermicreaction upon the application of the material to blood. Oftentimesexcess material is unnecessarily poured onto a wound, which canexacerbate the exothermic effects. Depending upon the specificattributes of the material, the resulting exothermia may be sufficientto cause discomfort to or even burn the patient. Although some prior artpatents specifically recite the resulting exothermia as being adesirable feature that can provide clotting effects to the wound thatare similar to cauterization, there exists the possibility that thetissue at and around the wound site may be undesirably impacted.

Furthermore, to remove such materials from wounds, irrigation of thewound is often required. If an amount of material is administered thatcauses discomfort or burning, the wound may require immediate flushing.In instances where a wounded person or animal has not yet beentransported to a facility capable of providing the needed irrigation,undesirable effects or over-treatment of the wound may result.

Bleeding can also be a problem during surgical procedures. Apart fromsuturing or stapling an incision or internally bleeding area, bleedingis often controlled using a sponge or other material used to exertpressure against the bleed site and/or absorb the blood. However, whenthe bleeding becomes excessive, these measures may not be sufficient tostop the blood flow. Moreover, any highly exothermic bleed-controlmaterial may damage the tissue surrounding the bleed site and may not beconfigured for easy removal after use.

Based on the foregoing, it is a general object of the present inventionto provide a hemostatic agent that overcomes or improves upon thedrawbacks associated with the prior art. It is also a general object ofthe present invention to provide devices capable of applying suchhemostatic agents.

SUMMARY OF THE INVENTION

According to one aspect, the present invention resides in a device forpromoting the clotting of blood, thereby controlling bleeding. Thedevice comprises a clay material in particle form and a receptacle forcontaining the clay material. At least a portion of the receptacle isdefined by a mesh having openings therein such that when the device isapplied to a bleed site, the particles of clay come into contact withblood through the openings.

According to another aspect, the present invention resides in anotherdevice capable of providing a hemostatic effect on a bleeding wound tocontrol blood flow from the wound. The device comprises a gauzesubstrate and a clay material disposed on the gauze substrate. Upon theapplication of the device to the bleeding wound, at least a portion ofthe clay material comes into contact with the blood to cause thehemostatic effect.

According to another aspect, the present invention resides in a bandagethat can be applied to a bleeding wound to promote the clotting ofblood, thereby controlling bleeding. The bandage comprises a substrate,a mesh mounted on the substrate, and particles of a clay materialretained in the mesh. The mesh is defined by a plurality of membersarranged to define openings that allow for the flow of blood into themesh and into the clay material, thereby producing a clotting effect.

According to another aspect, the present invention resides in ahemostatic sponge that can be applied to a bleeding wound to clot bloodand control bleeding. Such a sponge comprises a substrate, a hemostaticmaterial disposed on a first surface of the substrate, and a releaseagent disposed on a second surface of the substrate. The release agentis disposed on the wound-contacting surface of the substrate to inhibitthe adherence of the sponge to the wound tissue after clot formation.When treating a bleeding wound, application of the hemostatic spongecauses at least a portion of the hemostatic material to come intocontact with blood through the release agent and through the substrate.

According to yet another aspect, the present invention resides in otherforms of hemostatic sponges. In such forms the hemostatic sponge maycomprise a film and a hemostatic material incorporated into the film; asubstrate, a hemostatic material disposed on the substrate, and a filmdisposed over the hemostatic material; or a hemostatic materialsandwiched between two substrates.

According to yet another aspect, the present invention resides in ahemostatic device for promoting the clotting of blood, therebycontrolling bleeding. The device has a gauze substrate, a clay materialdisposed on the gauze substrate, and also a polyol such as glycerol orthe like disposed on the gauze substrate to bind the clay material. Whenthe device is used to treat a bleeding wound, at least a portion of theclay material comes into contact with blood emanating from the wound tocause the clotting.

According to yet another aspect, the present invention resides in abandage that can be applied to a bleeding wound to promote the clottingof blood, thereby controlling bleeding. The bandage has a flexiblesubstrate and a gauze substrate mounted thereon. The gauze substrateincludes a clay material and a polyol. When the bandage is used to treata bleeding wound, applying the bandage to the wound causes at least aportion of the clay material to come into contact with blood emanatingfrom the wound.

According to still another aspect, the present invention resides inhemostatic sponges. One type of sponge has a gauze substrate and adispersion of hemostatic material and a polyol on a first surface of thesubstrate. When this sponge is used to treat a bleeding wound, applyingthe sponge causes at least a portion of the hemostatic material to comeinto contact with blood. Another type of sponge has first and secondsubstrates. A hemostatic material is dispersed in the polyol and appliedto the first substrate, and the second substrate is placed on thehemostatic material dispersed in the polyol. When this sponge is used totreat a bleeding wound, applying the sponge causes at least a portion ofthe hemostatic material to come into contact with blood through at leastone of the substrates.

An advantage of the present invention is that unlike other materials,such as, for example zeolites, the clay component produces no exothermicreaction with blood. Eliminating the generation of heat at a wound siteis useful in minimizing discomfort and/or further injury to a patientand may be especially useful in the treatment of certain patients suchas pediatric or geriatric patients or when the wound being treated is ina particularly sensitive or delicate area.

Another advantage is that the clay can be finely divided and depositedon a multitude of surfaces, thereby facilitating its use as a componentin a variety of blood control devices. In particular, the clay can beused in particle form (e.g., retained in a mesh or in a film), or it canbe used in powder form (e.g., deposited on a fibrous substrate to form agauze or a sponge). In any embodiment, the efficacy of the clay inpromoting hemostasis at a wound site is improved over similar agentsthat can be used only in one form (e.g., as particles of a particularsize) to limit undesirable side effects such as excessive exothermicreactions.

Still another advantage of the present invention is that the devices andagents of the present invention are easily applied to open wounds.Particularly when the hemostatic agent is retained in a mesh or similardevice, or when it is incorporated into a woven structure to form agauze, the device can be readily removed from a sterilized packaging andplaced or held directly at the points from which blood emanates to causeclotting.

One advantage of the use of a polyol such as glycerol in conjunctionwith clay (or any other hemostatic agent) is that dust oftentimesassociated with the clay (or other hemostatic agent) is suppressed.Because of its low volatility, glycerol, for example, does not readilyevaporate. Because it does not readily evaporate, the generation of claydust when the clay is dispersed in the glycerol is mitigated. Mitigatingor suppressing the dust means that more hemostatic material is availablefor blood clotting purposes.

Another advantage of the use of a polyol in conjunction with clay (orother hemostatic agent) is that the undesirable adhesion of the spongeto the wound is reduced. Accordingly, the sponge or other device can beeasily removed from a wound without breaking a newly formed blood clot.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic representation of a mesh structure of a bloodclotting device of the present invention.

FIG. 2 is a side view of the blood clotting device of FIG. 1illustrating the retaining of clay particles in the mesh structure.

FIG. 3 is a perspective view of a blood clotting device thatincorporates a clay material into a gauze.

FIG. 4 is a perspective view of a blood clotting device thatincorporates a clay material into a cloth.

FIG. 5A is a perspective view of a bandage incorporating the clayparticles in a mesh container for application to a bleeding wound.

FIG. 5B is a perspective view of a bandage incorporating the hemostaticmaterial and a polyol into a gauze substrate for application to ableeding wound.

FIG. 6 is a schematic representation of a sponge having hemostaticcapabilities.

FIG. 7 is a schematic representation of another embodiment of a spongehaving hemostatic capabilities.

FIG. 8 is a schematic representation of another embodiment of a spongehaving hemostatic capabilities.

FIG. 9 is a schematic representation of another embodiment of a spongehaving hemostatic capabilities.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Disclosed herein are hemostatic devices and hemostatic agents that areapplicable to bleeding wounds to promote hemostasis. The hemostaticagents generally include clay materials or other silica-based materialsthat, when brought into contact with a bleeding wound, can minimize orstop blood flow by absorbing at least portions of the liquid phases ofthe blood, thereby facilitating clotting. The present invention is notlimited to clay, however, as other materials such as bioactive glasses,biological hemostats, molecular sieve materials, diatomaceous earth,combinations of the foregoing, and the like are within the scope of thepresent invention and can be used in conjunction with the clay orseparately as a hemostatic agent.

As used herein, the term “clay” refers to a crystalline form of hydratedaluminum silicate. The crystals of clay are irregularly shaped andinsoluble in water. The combination of some types of clay with water mayproduce a mass having some degree of plasticity. Depending upon the typeof clay, the combination thereof with water may produce a colloidal gelhaving thixotropic properties.

In one preferred embodiment of the present invention, the clay materialis kaolin, which includes the mineral “kaolinite.” Although the term“kaolin” is used hereinafter to describe the present invention, itshould be understood that kaolinite may also be used in conjunction withor in place of kaolin. The present invention is also not limited withregard to kaolin or kaolinite, however, as other materials are withinthe scope of the present invention. Such materials include, but are notlimited to, attapulgite, bentonite, combinations of the foregoing,combinations of the foregoing with kaolin and/or diatomaceous earth, andthe like.

As used herein, the term “kaolin” refers to a soft, earthyaluminosilicate clay (and, more specifically, to a dioctahedralphyllosilicate clay) having the chemical formula Al₂Si₂O₅(OH)₄. Kaolinis a naturally occurring layered silicate mineral having alternatingtetrahedral sheets and octahedral sheets of alumina octahedra linked viathe oxygen atoms of hydroxyl groups. Kaolin comprises about 50% alumina,about 50% silica, and trace impurities.

More preferably, the clay is Edgar's plastic kaolin (hereinafter “EPK”),which is a water-washed kaolin clay that is mined and processed in andnear Edgar, Fla. Edgar's plastic kaolin has desirable plasticitycharacteristics, is castable, and when mixed with water produces athixotropic slurry.

The kaolin material of the present invention may be mixed with orotherwise used in conjunction with other materials to provide additionalclotting functions and/or improved efficacy. Such materials include, butare not limited to, magnesium sulfate, sodium metaphosphate, calciumchloride, dextrin, combinations of the foregoing materials, and hydratesof the foregoing materials.

Various materials may be mixed with, associated with, or incorporatedinto the kaolin to maintain an antiseptic environment at the wound siteor to provide functions that are supplemental to the clotting functionsof the clay. Exemplary materials that can be used include, but are notlimited to, pharmaceutically-active compositions such as antibiotics,antifungal agents, antimicrobial agents, anti-inflammatory agents,analgesics, antihistamines (e.g., cimetidine, chlorpheniramine maleate,diphenhydramine hydrochloride, and promethazine hydrochloride),compounds containing silver or copper ions, combinations of theforegoing, and the like. Other materials that can be incorporated toprovide additional hemostatic functions include ascorbic acid,tranexamic acid, rutin, and thrombin. Botanical agents having desirableeffects on the wound site may also be added.

For use in the present invention, the kaolin (or other clay material ordiatomaceous earth) is preferably in particle form. As used herein,“particles” include beads, pellets, granules, rods, or any other surfacemorphology or combination of surface morphologies. Irrespective of thesurface morphology, the particles are about 0.2 mm (millimeters) toabout 10 mm, preferably about 0.5 mm to about 5 mm, and more preferablyabout 1 mm to about 2 mm in effective diameter. The present invention isnot limited in this regard, however, and other particle sizes (e.g.,less than about 0.2 mm) are also within the scope of the presentinvention. The particle size of the kaolin (or other clay material ordiatomaceous earth) may be so small so as to be considered powder. Ifthe particle size is considered to be powder, the powder may beimpalpable (i.e., tactilely undetectable).

The clay particles can be produced by any of several various methods.Such methods include mixing, extrusion, spheronizing, and the like.Equipment that can be utilized for the mixing, extruding, orspheronizing of the clay is available from Caleva Process Solutions Ltd.in Dorset, United Kingdom. Other methods include the use of a fluid bedor a pelletizing apparatus. Fluid beds for the production of clayparticles are available from Glatt Air Technologies in Ramsey, N.J. Diskpelletizers for the production of clay particles are available fromFeeco International, Inc., in Green Bay, Wis. Preferably, the clay isextruded through a suitable pelletizing device. The present invention isnot limited in this regard, however, as other devices and methods forproducing particlized clay are within the scope of the presentinvention.

The EPK used in the present invention is particlized, dried, and firedto about 600 degrees C. In order to achieve a suitably homogenousmixture of the EPK to form the particles, a relatively high shear isapplied to a mass of the EPK using a suitable mixing apparatus. Prior toshearing, the water content of the clay is measured and adjusted to beabout 20% by weight to give a sufficiently workable mixture forextrusion and subsequent handling.

During the firing of the EPK to about 600 degrees C., the material isvitrified. Vitrification is effected via repeated melting and coolingcycles to allow the EPK (or other clay material) to be converted into aglassy substance. With increasing numbers of cycles, the crystallinestructure is broken down to result in an amorphous composition. Theamorphous nature of the EPK allows it to maintain its structuralintegrity when subsequently wetted. As a result, the EPK maintains itsstructural integrity when wetted during use, for example, when appliedto blood. The present invention is not limited to the use of vitrifiedclays, however, as clay material that has not been vitrified is stillwithin the scope of the present invention. In particular, unvitrifiedclay can still be applied to a bleeding wound to provide hemostasis.

It is believed that the cellular clotting mechanism of clay activatescertain contact factors when applied to blood. More specifically, it isbelieved that kaolin (particularly EPK) initiates mechanisms by whichwater in blood is absorbed to facilitate clotting functions.

Referring now to FIG. 1, one embodiment of a hemostatic device intowhich the kaolin in particle form is incorporated is shown. The deviceis a permeable pouch that allows liquid to enter to contact the kaolinparticles retained therein. Sealed packaging (not shown) provides asterile environment for storing the hemostatic device until it can beused. The device, which is shown generally at 10 and is hereinafterreferred to as “pouch 10,” comprises a screen or mesh 12 and theparticlized kaolin 14 retained therein by the screen or mesh. The mesh12 is closed on all sides and defines openings that are capable ofretaining the particlized kaolin 14 therein while allowing liquid toflow through. As illustrated, the mesh 12 is shown as being flattenedout, and, by way of example, only a few particles of particlized kaolin14 are shown. The particlized kaolin 14 may be blended with particles ofother types of clay, diatomaceous earth, and the like to form ahomogenous mixture.

The mesh 12 is defined by interconnected strands, filaments, or stripsof material. The strands, filaments, or strips can be interconnected inany one or a combination of manners including, but not limited to, beingwoven into a gauze, intertwined, integrally-formed, and the like.Preferably, the interconnection is such that the mesh can flex whilesubstantially maintaining the dimensions of the openings definedthereby. The material from which the strands, filaments or strips arefabricated may be a polymer (e.g., nylon, polyethylene, polypropylene,polyester, or the like), metal, fiberglass, or an organic substance(e.g., cotton, wool, silk, or the like).

Referring now to FIG. 2, the openings defined by the mesh 12 are sizedto retain the particlized kaolin 14 but permit the flow of bloodtherethrough. Because the mesh 12 may be pulled tight around theparticlized kaolin 14, the particles may extend through the openings bya distance d. If the particles extend through the openings, they willdirectly contact tissue against which the pouch 10 is applied. Thus,blood emanating from the tissue immediately contacts the particlizedkaolin 14, and the water phase thereof is wicked into the kaolin,thereby facilitating the clotting of the blood. However, it is not arequirement of the present invention that the particles protrude throughthe mesh.

To apply the pouch 10 to a bleeding wound, the pouch is removed from thepackaging and placed on the bleeding wound. The particlized kaolin 14 inthe mesh 12 contacts the tissue of the wound and/or the blood emanatingfrom the wound, and at least a portion of the liquid phase of the bloodis absorbed by the clay material, thereby promoting clotting. Theflexibility of the mesh 12 allows the mesh to conform to the shape ofthe bleeding wound and to retain that shape upon application.

Referring now to FIG. 3, another embodiment of a hemostatic device ofthe present invention is a kaolin gauze, which is shown generally at 20and is hereinafter referred to as “gauze 20.” Kaolin is coated onto agauze substrate using any suitable method to result in the gauze 20. Oneexemplary method of coating kaolin onto the gauze substrate is toimmerse the substrate in a kaolin/water slurry. The kaolin material usedfor the slurry is preferably finely ground kaolin powder, although thepresent invention is not limited in this regard as kaolin particles,flakes, chips, beads, rods, granules, or the like may alternatively oradditionally be used. The gauze substrate may be any suitable woven ornon-woven fibrous material including, but not limited to, cotton, silk,wool, plastic, cellulose, rayon, polyester, combinations of theforegoing, and the like. The present invention is not limited to wovenor non-woven fibrous materials as the gauze substrates, however, asfelts and the like are also within the scope of the present invention.

The gauze 20 of the present invention is not limited to kaolin, however,as other clays such as attapulgite, bentonite, and combinations thereofmay be used in place of or in addition to the kaolin. Furthermore, othersilica-based materials such as bioactive glasses, diatomaceous earth,combinations of the foregoing, and the like may also be utilized inaddition to or in place of any of the foregoing clay materials.

Once the kaolin is dried onto the gauze substrate to form the gauze 20,the gauze is sufficiently flexible to allow the gauze to be folded,rolled, or otherwise manipulated for packaging.

The flexibility of the substrate of the gauze 20 allows the gauze toform to a shape of the bleeding wound and to retain the shape of thebleeding wound upon application.

One manner of depositing the kaolin (or other clay) coating on the gauzesubstrate includes heating the kaolin/water slurry. Preferably, theslurry is heated to boiling because higher temperatures tend tofacilitate the adhesion of the kaolin to the substrate. The presentinvention is not limited in this regard, however, as the slurry may beheated to a lower temperature depending on the desired characteristicsof the kaolin coating. Boiling the slurry also provides an effectiveform of agitation that uniformly disperses the kaolin in the liquidphase.

The substrate is then immersed in the boiling slurry for an amount oftime sufficient to cause the kaolin to deposit onto the substrate. Giventhe rheology of wetted kaolin and the material from which the gauze orsubstrate is fabricated, the kaolin may adhere as a film directly to thesurfaces of the substrate, or it may agglomerate in the interstices ofthe strands as well as along the strands themselves, thereby beingtrapped in the fiber matrix.

Another manner of depositing the kaolin coating on the substrateincludes applying the kaolin in slurry form on one side of the gauzesubstrate using a spraying technique, a slot die technique, or acombination thereof. In using any technique, the amount of slurryapplied to the gauze substrate is limited to avoid or at least minimizethe saturation of the substrate. Preferably, a colloidal form of thekaolin (or other clay) is used to provide a stable suspension of thematerial with suitable viscosity for application using the slot dietechnique.

Once sprayed or applied using the slot die technique, the coated gauzesubstrate is then rolled or scraped to further embed the kaolin into thematerial of the substrate. The gauze substrate is then dried.

In some embodiments, the kaolin may be attached to the gauze substrateusing a binder. In embodiments in which a binder is used, the materialof the binder is compatible with biological tissue. Preferred bindersinclude polyols, chitosan, and polyvinyl alcohol, all of which haveadhesive qualities and are compatible with biological tissue. At leastchitosan exhibits hemostatic properties.

One exemplary method for the production of this device may comprise thesteps of unwinding gauze from a roll, immersing the gauze in a slurry ofhemostatic material and water, applying pressure to the gauze by rollingthe wet gauze under high pressure to incorporate the hemostatic materialinto the material of the gauze, drying the rolled, wet gauze, andremoving dust from the gauze (e.g., via blasting with air knives or airnozzles, through the use of electrostatic energy, vacuuming, or brushingwith direct contact brushes). Following the removal of dust from thegauze, the gauze back may be wound back onto a roll, or it may be cutinto sheets for individual packaging.

One or more variables may be manipulated to optimize the amount andintegrity of the kaolin retained on the gauze. These variables include,but are not limited to, slurry temperature, immersion time, the slurryagitation method, and the type of liquid (of the slurry). The elevationof the slurry temperature, as indicated above, aids in the retention ofthe kaolin on the gauze. The agitation may be effected by forcing air orother gas through nozzles, stirring, bubbling, boiling, or ultrasonicvibration.

The liquid used for the slurry may also be something other than water.For example, the liquid may be an aqueous ammonia solution. Aqueousammonia has been found to induce swelling in certain fibrous materials,such as the materials typically utilized to fabricate gauze.

In embodiments in which a polyol is used in the gauze 20, the polyol maybe glycerol (also known as glycerin, glycerine, glyceritol, glycylalcohol, and by its chemical name propane-1,2,3-triol). Glycerol is alubricious, hygroscopic, water-soluble liquid that is compatible withbiological tissue. The kaolin is dispersed in the glycerol to form adispersion or otherwise mixed with the glycerol and is deposited ontothe gauze substrate using any suitable method. Suitable methods fordepositing the kaolin/glycerol dispersion onto the gauze substrateinclude, but are not limited to, spraying the dispersion, soaking thegauze substrate in the dispersion, application via slot die techniques,physical means such as brushing or rolling the dispersion onto thegauze, and the like.

The present invention is not limited to the use of glycerol, however, asother glycerol-based compounds including glycerol alcohols (e.g.propylene glycols), glycerol-based esterified fatty acids (e.g.,glyceryl triacetates), and other materials having humectant propertiesand the like (as well as combinations of the foregoing) are within thescope of the present invention. Furthermore, other polyols such assorbitol, xylitol, maltol, combinations of the foregoing, and the likeas well as polymeric polyols (e.g., polydextrose) are also within thescope of the present invention.

Referring now to FIG. 4, another embodiment of a hemostatic device ofthe present invention is a cloth having hemostatic properties, showngenerally at 20, and which is hereinafter referred to as “cloth 30.” Thecloth 30 is a fabric which may be defined by woven or unwoven strands ora felt or the like into which a biological hemostatic material isinfused or impregnated. Hemostatic materials that may be infused orimpregnated into the fabric of cloth 30 include, but are not limited to,clays (such as kaolin) in the form of particles 32, other silica-basedmaterial (such as diatomaceous earth, combinations thereof, or thelike), chitosan, combinations of the foregoing, and the like. Inembodiments in which such materials are infused or impregnated into acloth, the material is preferably incorporated into the cloth in ahydrated state and subsequently dried.

In either gauze or cloth embodiments, the gauze or cloth material may becross-linked with a polysaccharide or similar material.

Referring now to FIG. 5A, another embodiment of the present invention isa bandage, shown at 50, which comprises particlized kaolin 14 (or someother clay material or diatomaceous earth) retained in the mesh 12 andmounted to a flexible substrate 52 that can be applied to a wound (forexample, using a pressure-sensitive adhesive to adhere the bandage 50 tothe skin of a wearer). The mesh 12 is stitched, glued, or otherwisemounted to a substrate 52 to form the bandage 50.

The substrate 52 is a plastic or a cloth member that is conducive tobeing retained on the skin of an injured person or animal on orproximate a bleeding wound. An adhesive 54 is disposed on a surface ofthe substrate 52 that engages the skin of the injured person or animal.Particularly if the substrate 52 is a non-breathable plastic material,the substrate may include holes 56 to allow for the dissipation ofmoisture evaporating from the skin surface.

Referring now to FIG. 5B, another embodiment of the bandage is shown at150. The bandage 150 comprises particlized kaolin (or some other claymaterial or diatomaceous earth capable of imparting a hemostaticfunction) dispersed in glycerol and applied to a gauze substrate 112.The gauze substrate 112 is mounted to a flexible substrate 152 that canbe applied to a wound (for example, using a pressure-sensitive adhesive154 disposed over substantially all of a skin-contacting surface of theflexible substrate 152 to adhere the bandage 150 to the skin of awearer). The gauze substrate 112 is stitched, glued, or otherwisemounted to the substrate 152, which may be a plastic or cloth memberthat may include holes 156. A release agent (e.g., polyvinyl alcohol,glycerol, carboxymethyl cellulose, or the like) may be disposed over thekaolin/glycerol dispersion on the gauze substrate 112.

Referring now to FIG. 6, another embodiment of the present invention isa sponge, shown at 60, which comprises a substrate 62, the particlizedkaolin 14 (or some other clay material or diatomaceous earth) disposedon one face of the substrate 62, and a release agent 64 disposed on anopposing face of the substrate. The sponge 60 allows for sufficientcontact of the particlized kaolin 14 with blood emanating from a woundand through the release agent 64 and the substrate 62 while minimizingthe adhesion of the sponge to the wound tissue. The sponge 60 is alsocompatible with living tissue.

The substrate 62 is an absorbent gauze material that defines a matrix.The present invention is not so limited, however, as other materialssuch as rayon/polyester cellulose blends and the like are also withinthe scope of the present invention. Other materials from which thesubstrate 62 may be fabricated include woven fabric, non-woven fabric,paper (e.g., kraft paper and the like), and cellulose material (e.g.,cotton in the forms of balls, swabs, and the like). Any material fromwhich the substrate 62 may be fabricated may have an elastic quality.When elastic materials are used as the substrate 62, the sponge 60becomes both a hemostatic device and a pressure bandage, particularly inembodiments in which a surface cohesive agent or mechanical fastener isadded to secure the sponge in place over a wound.

The hemostatic agent used in the sponge 60 is not limited to particlizedkaolin 14. Other materials such as attapulgite, bentonite, combinationsof the foregoing, or a combination of the foregoing with kaolin may beused. The present invention is also not limited to clays, as othermaterials such as bioactive glass, biological hemostats, diatomaceousearth, combinations thereof, the combinations thereof with clay are alsowithin the scope of the present invention.

The particlized kaolin 14 may be bound to the substrate 62 via coulombicforces, by impregnating or otherwise incorporating the clay or otherhemostatic material directly into the material of the substrate, byusing a binder, by trapping the hemostatic material within the matrix,or the like.

When using a binder to bind the particlized kaolin 14 to the substrate62, the binder material may provide additional functionality to thesponge 60. Materials from which the binder may be fabricated include,but are not limited to, chitosan, polyvinyl alcohol, guar gum,gelatinized starches, polysaccharides, cellulose, calcium alginate, andthe like, as well as combinations of the foregoing.

In embodiments in which the particlized kaolin 14 is incorporated intothe substrate 62 directly, the particlized kaolin may be added duringthe substrate fabrication. If the substrate is a non-woven gauzematerial containing rayon and polyester, then the particlized kaolin 14may be incorporated into or onto the fibers of rayon and polyester. Forexample, the particlized kaolin 14 may be in powder form and applied tomolten polyester, and polyester fibers may be drawn from thepolyester/hemostatic material melt. If the substrate is a woven gauze(e.g., cotton), the kaolin 14 in powder form may be incorporated intothe cotton threads during formation of the threads.

The particlized kaolin 14 may also be dispersed in glycerol and appliedto the substrate 62 via a spray technique, a slot die technique,soaking, brushing, rolling, or the like.

The release agent 64 is a material that is disposed on thewound-contacting side of the substrate 62 to facilitate the easy removalof the sponge 60 from the wound tissue after the formation of bloodclots. The release agent 64 may be a continuous film, or it may bediscontinuous on the surface of the substrate. One material that may beused as a release agent is polyvinyl alcohol, which is a biocompatiblematerial that may be formed as a thin film and that does notsignificantly affect the absorbency and liquid permeability of thesponge 60. Another material that may be used as the release agent 64 isglycerol, which may be applied in addition to particlized kaolin 14dispersed in glycerol. When applied as the release agent 64, theglycerol forms a film over the dispersion of the particlized kaolin 14in glycerol. Other materials that may be utilized as release agentsinclude, but are not limited to, carboxymethyl cellulose. In anyconfiguration of the sponge 60, the release agent 64 may be applieddirectly to the wound-contacting surface of the substrate 62.

In the alternative, the release agent 64 may be applied to the non-woundcontacting surface of the substrate 62 as a slurry of clay and releaseagent. In such an embodiment, the concentration of the polyvinyl alcoholor glycerol is such that at least some of the alcohol component thereofseeps to the wound-contacting surface of the substrate 62, while theclay material remains on or near the non-wound contacting surface. Inany embodiment, the polyvinyl alcohol or the glycerol serves not only asa release agent, but as an agent that suppresses the dust of theparticlized kaolin 14.

Other materials that may be used as release agents that are within thescope of the present invention include, but are not limited to, siliconeand gelatinized starches. As with polyvinyl alcohol and glycerol, eithermay be applied in film form.

The sponge 60 may further include a component that imparts a radiopaquecharacteristic to the sponge. In such an embodiment, barium sulfate maybe incorporated into a slurry that includes the particlized kaolin 14and applied to the substrate 62.

The sponge 60 may further include water or alcohol, thereby allowing thesponge to be used as a wipe.

Referring now to FIG. 7, another embodiment of a sponge is showngenerally at 160. The sponge 160 comprises a film 162 into whichparticlized kaolin 14 is dispersed. The physical integrity of the sponge160 is maintained by the film 162. Preferably, the material from whichthe film 162 is fabricated is polyvinyl alcohol. In fabricating thesponge 160, the particlized kaolin 14 is dispersed into polyvinylalcohol, which is then formed into a sheet. The sponge 160 is especiallyuseful when incorporated into a bandage.

Referring now to FIG. 8, another embodiment of a sponge is showngenerally at 260. The sponge 260 comprises a substrate 262, particlizedkaolin 14 disposed on the substrate, and a film 266 disposed over thehemostatic material. The particlized kaolin 14 is unbound (without abinder) blood coagulating agent and is preferably disposed on thesubstrate 262 in strips to facilitate the folding of the sponge 260. Thefilm 266 is polyvinyl alcohol, glycerol, or the like and is applied toboth contain the particlized kaolin 14 and to minimize the generation ofdust. Upon application to a bleeding wound, blood from the wound iswicked into the substrate 262 and contacts the particlized kaolin 14.

Referring now to FIG. 9, another embodiment of a sponge is showngenerally at 360. The sponge 360 comprises particlized kaolin 14sandwiched between two substrates 362. The substrates 362 can be boundtogether in any suitable manner such as heat sealing through areasselectively absent of particlized kaolin 14, using an adhesive or binderin select areas, applying a containment film of material (such aspolyvinyl alcohol) over the entire sponge 360, or a combination of anyof the foregoing. The particlized kaolin 14 can also be used inconjunction with glycerol, e.g., by being dispersed in glycerol andapplied to the sponge 360.

The sponge 60 (as well as the sponges shown at 160, 260, and 360) may befolded and used in various manners. The sponge 60 may be folded suchthat the surfaces on which the particlized kaolin 14 is disposed are onthe inside surfaces of the folded sponge, so as to minimize problems ofdusting and detachment of the hemostatic material from the substrate 62.The sponge 60 (and the sponges 160, 260, and 360) can also be foldedinto a pleated form or into a configuration to produce a number ofdistinct plies attached along the edges. By configuring the sponge 60 insuch a manner, the compliancy and absorbency requirements of differentapplications can be addressed. The sponge 60 can also be cut or formedinto elongated strips for wrapping over the wounds of an injured personor animal or for incorporation into cylinders or swabs. The sponge 60can also be cut, ripped, ground, or otherwise formed into small piecesfor applications such as stuffing into mesh containers.

Example 1—The Effect of Slurry Temperature on the Ability of CottonGauze to Retain Kaolin Clay

Temperatures of kaolin/water slurries were varied to assess the abilityof cotton gauze to retain kaolin clay. Slurries of water and EPK wereprepared in which the kaolin was 40% of the total weight of the slurry.Three sponges were made (one from each piece of gauze) by immersing thecotton gauzes into the slurries of varying temperatures, rolling the wetsponges under pressure, and drying. The Table below indicates theparameters for each slurry and the results obtained.

Slurry Starting Gauze Temp. gauze weight (degrees Agitation weight after% kaolin Sample C.) method (grams) (grams) (wt. %) 1 22 Stir 3.139 5.5944 1 minute 2 90 Stir 3.064 5.868 48 1 minute 3 100 Boil 3.085 6.481 521 minute

The gauze weight after is the weight of the gauze after rolling anddrying. It was noted that the elevated slurry temperature increased theamount of retained kaolin. One theory for this is that the cotton fiberstructure of the gauze is loosened and swollen by its immersion in thehot liquid.

Example 2—Application of Dry Kaolin to Dry Cotton Gauze to FormHemostatic Device

Dry kaolin was applied to a dry cotton gauze. The gauze was then rolled.The amount of kaolin retain on the gauze was visibly and significantlyless than the amount of kaolin retained on the gauze of Sample 3(Example 1). This sample, however, accelerated the clot time in sheepwhole blood by 70% over the unaccelerated clot time of the blood.

Example 3—Reduction of Kaolin Dust Using Glycerol

A slurry of 50 grams (g) of water, 20 g of glycerol, and 15 g of kaolinpowder was prepared and used to saturate a gauze sponge (Kendall Curity2733). The saturated gauze sponge was dried. The sponge was held andtapped with a pencil over a clean glass surface. A visual determinationindicated that no readily discernible dust was removed from the spongeas a result of the tapping.

A second sponge was prepared without glycerol and dried. The secondsponge was held and tapped with a pencil over a clean glass surface. Avisual determination indicated that a substantial amount of kaolin dustwas removed from the second sponge as a result of the tapping.

Although this invention has been shown and described with respect to thedetailed embodiments thereof, it will be understood by those of skill inthe art that various changes may be made and equivalents may besubstituted for elements thereof without departing from the scope of theinvention. In addition, modifications may be made to adapt a particularsituation or material to the teachings of the invention withoutdeparting from the essential scope thereof. Therefore, it is intendedthat the invention not be limited to the particular embodimentsdisclosed in the above detailed description, but that the invention willinclude all embodiments falling within the scope of the appended claims.

The following is claimed:
 1. A method for manufacturing a hemostaticdevice comprising: providing an absorbent substrate; applying a claymaterial that is distinct from the substrate to a surface of thesubstrate; applying a binder comprising glycerol that is distinct fromthe substrate to the substrate to adhere at least a portion of the claymaterial to the surface of the substrate so that the surface issubstantially free of loose clay; wherein the clay material ispositioned on the surface of the device in a region configured tocontact blood from a bleeding wound, thereby promoting clotting; whereinthe hemostatic device is configured to absorb blood from the bleedingwound.
 2. The method of claim 1, wherein the clay material is selectedfrom the group consisting of attapulgite, bentonite, kaolin, andcombinations of the foregoing materials.
 3. The method of claim 1,wherein the clay comprises kaolin.
 4. The method of claim 1, wherein theclay material and the binder are applied as a single step.
 5. The methodof claim 1, wherein the absorbent substrate is fabricated from amaterial selected from the group consisting of cotton, silk, wool,plastic, cellulose, rayon, polyester, and combinations of the foregoing.6. The method of claim 1, wherein the absorbent substrate is flexible toallow the absorbent substrate to form to a shape of the bleeding woundand to retain the shape of the bleeding wound.
 7. The method of claim 1,wherein the binder is applied to the absorbent substrate by a sprayingprocess.
 8. The method of claim 1, wherein the binder and the claymaterial are applied to the absorbent substrate by a spraying process.9. The method of claim 1, wherein the binder is applied to the absorbentsubstrate by immersing the absorbent substrate in a liquid comprisingthe binder.
 10. The method of claim 1, wherein the binder and the claymaterial are applied to the absorbent substrate by a slot-die technique.11. The method of claim 1, wherein the binder and the clay material areapplied to the absorbent substrate by rolling the binder and the claymaterial on the absorbent substrate.
 12. A method for manufacturing ahemostatic device comprising: providing an absorbent substrate; applyinga clay material that is distinct from the substrate to a surface of thesubstrate; applying a binder comprising an alginate that is distinctfrom the substrate to a surface of the substrate to adhere at least aportion of the clay material to the surface of the substrate so that thesurface is substantially free of loose clay; wherein the clay materialis positioned on the surface of the device in a region configured tocontact blood from a bleeding wound, thereby promoting clotting; whereinthe hemostatic device is configured to absorb blood from the bleedingwound.
 13. The method of claim 12, wherein the clay material is selectedfrom the group consisting of attapulgite, bentonite, kaolin, andcombinations of the foregoing materials.
 14. The method of claim 12,wherein the clay comprises kaolin.
 15. The method of claim 12, whereinthe clay material and the binder are applied as a single step.
 16. Themethod of claim 12, wherein the absorbent substrate is fabricated from amaterial selected from the group consisting of cotton, silk, wool,plastic, cellulose, rayon, polyester, and combinations of the foregoing.17. The method of claim 12, wherein the absorbent substrate is flexibleto allow the absorbent substrate to form to a shape of the bleedingwound and to retain the shape of the bleeding wound.
 18. The method ofclaim 12, wherein the binder is applied to the absorbent substrate by aspraying process.
 19. The method of claim 12, wherein the binder and theclay material are applied to the absorbent substrate by a sprayingprocess.
 20. The method of claim 12, wherein the binder is applied tothe absorbent substrate by immersing the absorbent substrate in a liquidcomprising the binder.
 21. The method of claim 12, wherein the binderand the clay material are applied to the absorbent substrate by aslot-die technique.
 22. The method of claim 12, wherein the binder andthe clay material are applied to the absorbent substrate by rolling thebinder and the clay material on the absorbent substrate.